Receptors play a fundament role in both normal biological and pathological processes. Receptors generally bind a molecule and transduce the original signal produced upon binding of the molecule into a biological response by way of a cascade of intracellular signalling molecules.
In many cases, the binding of a molecule to a receptor modulates the activity of a number of intracellular signalling pathways, each of which may result in a specific biological response. For example, binding of the TNF-α to TNF Receptor-1 (TNFR1) activates multiple intracellular signalling pathways, including the p38, JNK and ERK1/2 signalling pathways.
In this regard, activation of p38 signalling by TNF receptor-1 upon binding of TNF-α is associated with an anti-inflammatory response and killing of tumour cells. Activation of the JNK and ERK1/2 pathways upon binding of TNF-α is important, for example, for cell regeneration. However, activation of the JNK and/or ERK1/2 signalling pathways is also associated with pathogenetic responses. This example underscores the fact that in many circumstances the modulation of multiple signalling pathways produces both beneficial and unwanted biological responses.
Given that receptors and their intracellular signalling pathways play a fundamental in both the biology of normal and pathological processes, receptor activity and intracellular signalling are potential targets for therapeutic intervention. However, a deficiency with many drugs that modulate receptor activity and/or the activity of their intracellular signalling pathways is that the drugs do not have the capacity to selectively target one or more intracellular signalling pathways, and as such promiscuously modulate other signalling pathways.
Accordingly, there is a need for new therapeutic agents and new therapeutic strategies that have the capacity to selectively target specific intracellular signalling pathways. The present invention relates to a method of selectively modulating signalling through a receptor that is involved in signalling through multiple intracellular signalling pathways.
A reference herein to a patent document or other matter which is given as prior art is not to be taken as an admission that that document or matter was known or that the information it contains was part of the common general knowledge as at the priority date of any of the claims.